Latin America: the next region for haematopoietic transplant progress.

Haematopoietic cell transplant activity in the 28 countries comprising Latin America is poorly defined. We conducted a voluntary survey of members of the Latin American Bone Marrow Transplantation Group regarding transplant activity 2009-2012. Collated responses were compared with data of transplant rates from the Worldwide Network for Blood and Marrow Transplantation for other geographic regions. Several socio-economic variables were analysed to determine correlations with transplant rates. In total, 94 teams from 12 countries reported 11 519 transplants including 7033 autotransplants and 4486 allotransplants. Annual activity increased from 2517 transplants in 2009 to 3263 in 2012, a 30% increase. Median transplants rate (transplant per million inhabitants) in 2012 was 64 (autotransplants, median 40; allotransplants, median 24). This rate is substantially lower than that in North America and European regions (482 and 378) but higher than that in the Eastern Mediterranean and Asia Pacific regions (30 and 45). However, the Latin America transplant rate is 5-8-fold lower than that in America and Europe, suggesting a need to increase transplant availability. Transplant team density in Latin America (teams per million population; 1.8) is 3-4-fold lower than that in North America (6.2) or Europe (7.6). Within Latin America, there is substantial diversity in transplant rates by country partially explained by diverse socio-economic variables including per capita gross national income, health expenditure and physician density. These data should help inform future health-care policy in Latin America.

Modulation of theta/alpha frequency profiles of slow auditory-evoked responses in the songbird zebra finch.

Spatiotemporal patterns of forebrain neural activity associated with auditory perception of biologically relevant complex acoustic stimuli can be conveniently studied in the songbird zebra finch. Here we present a time-frequency analysis of averaged slow auditory-evoked potentials (sAEPs) obtained at electrode locations overlying the main song control nucleus, high vocal center. Gabor spectrograms of these sAEPs show a prolonged response time course consisting of unimodal frequency peaks in the theta/alpha range (4-17 Hz). There is a stimulus-dependent modulation of the duration of the response and of the total number of its constituent frequency peaks, an effect that is bilateral in 75% of the birds and lateralized to the left side in the remaining 25%. Since the state of alertness of birds modulates these parameters along a similar continuum, these findings suggest that modulation of sAEP frequency profile may be dependent on attentional mechanisms. The presence and modulation of neurobiologically ubiquitous dominant frequency components also implicate the possible role of induced cerebral neuronal circuit oscillations in songbird auditory perception.

Development and adult phase plasticity of syllable repetitions in the birdsong of captive zebra finches (Taeniopygia guttata).

Oscines learn their birdsongs from tutors. The authors found that a small fraction (approximately 7%) of captive male zebra finches (Taeniopygia guttata) produce variant acoustic birdsong profiles consisting of repetitions of single song syllables at high frequencies. Juvenile offspring of nonrepeaters can selectively learn the syntactic rule or habit of repeating syllables from repeaters. Adult tutored syllable repeaters, unlike spontaneous repeaters, undergo a form of song plasticity involving progressive reduction of the mean number and variance of repeated syllables as a function of long-term exposure to nonrepeater songs without altering the number or sequence of syllables within motifs. These findings suggest that aspects of song syntax or temporal frame can be acquired independently of song syllable or spectral content, and plasticity involving restorative alteration of acquired variant temporal frames can occur after the closure of the critical period for song learning.

Immunity of patients surviving 20 to 30 years after allogeneic or syngeneic bone marrow transplantation.

The duration of immunodeficiency following marrow transplantation is not known. Questionnaires were used to study the infection rates in 72 patients surviving 20 to 30 years after marrow grafting. Furthermore, in 33 of the 72 patients and in 16 donors (siblings who originally donated the marrow) leukocyte subsets were assessed by flow cytometry. T-cell receptor excision circles (TRECs), markers of T cells generated de novo, were quantitated by real-time polymerase chain reaction. Immunoglobulin G(2) (IgG(2)) and antigen-specific IgG levels were determined by enzyme-linked immunosorbent assay. Infections diagnosed more than [corrected] 15 years after transplantation occurred rarely. The average rate was 0.07 infections per patient-year (one infection every 14 years), excluding respiratory tract infections, gastroenteritis, lip sores, and hepatitis C. The counts of circulating monocytes, natural killer cells, B cells, CD4 T cells, and CD8 T cells in the patients were not lower than in the donors. The counts of TREC(+) CD4 T cells in transplant recipients younger than age 18 years (at the time of transplantation) were not different from the counts in their donors. In contrast, the counts of TREC(+) CD4 T cells were lower in transplant recipients age 18 years or older, even in those with no history of clinical extensive chronic graft-versus-host disease, compared with their donors. The levels of total IgG(2) and specific IgG against Haemophilus influenzae and Streptococcus pneumoniae were similar in patients and donors. Overall, the immunity of patients surviving 20 to 30 years after transplantation is normal or near normal. Patients who received transplants in adulthood have a clinically insignificant deficiency of de novo-generated CD4 T cells, suggesting that in these patients the posttransplantation thymic insufficiency may not be fully reversible.

Reduction of female-directed song motifs induced by repeated singing in laboratory-bred zebra finches.

Songbirds such as zebra finches show a remarkable degree of neural plasticity associated with the motor act of singing. Here we show that in adult male zebra finches repeated female-directed singing episodes are associated with a change in subsequent singing behavior involving a progressive long-lasting decline in the number of song motifs sung. This reduction in song motif production cannot be completely explained by the circadian rhythm, declining motivation or neuromuscular exhaustion. Paired song induction sessions reveal that the time course of motif reduction during repeated singing can be best explained by the cumulative effect of reduction produced by each singing episode. These results suggest that song production in zebra finches is prone to a form of rapid behavioral adaptation.

Assessment of myocardial hypertrophy by echocardiography in adult patients receiving tacrolimus or cyclosporine therapy for prevention of acute GVHD.

The incidence of myocardial hypertrophy was determined in a comparative study of tacrolimus-based immunosuppression with cyclosporine-based immunosuppression for prevention of acute graft-versus-host disease (GVHD) after unrelated donor bone marrow transplantation. Patients were evaluated for clinical and echocardiographic abnormalities at baseline (prior to pretreatment conditioning and the first dose of study drug) and at 5-8 weeks after transplant when stable levels of oral tacrolimus or cyclosporine had been achieved. Left ventricular geometry and performance were assessed by echocardiography which included 2-D measurements and one Doppler measurement. Derived echocardiographic measurements and left ventricular mass index (LVMI) were also determined. A cut-off of <111 g/m(2) was used for the upper limit of normal for LVMI. Forty-four patients were included in this study (21 tacrolimus and 23 cyclosporine), of which 31 were evaluable for a comparison with both baseline and post-transplant values. There was no significant difference in the changes from baseline for mean left ventricular mass (LVM) or LVM index (LVMI) between treatment groups. Also, within the tacrolimus group there were no significant changes for these variables from baseline to post-transplant evaluations. Within the cyclosporine group there were significant increases from baseline for mean LVM (P = 0.011) and LVMI (P = 0.007). The incidence of myocardial hypertrophy (change of LVMI from <111 g/m(2) baseline to >111 g/m(2) post transplant) was 20% in the tacrolimus group and 56% in the cyclosporine group (P = 0.109). Changes in the LVMI from baseline to post baseline were greater with cyclosporine than with tacrolimus therapy, and there was no evidence that tacrolimus causes myocardial hypertrophy or significant clinical changes in adult bone marrow transplant patients. The increase in LVMI after transplant in the cyclosporine group was greater than in the tacrolimus group but was not associated with any significant clinical events.

Low B-cell and monocyte counts on day 80 are associated with high infection rates between days 100 and 365 after allogeneic marrow transplantation.

To ascertain which mononuclear cell subset deficiency plays a role in the marrow transplant recipient's susceptibility to infections, mononuclear cell subset counts were prospectively determined in 108 patients on day 80. Infections occurring between day 100 and 365 were recorded by an investigator blinded to the subset counts. In univariate analyses, the counts of the following subsets showed a significant inverse correlation with infection rates: total B cells, IgD(+) B cells, IgD(-) B cells, total CD4 T cells, CD28(+) CD4 T cells, CD28(-) CD4 T cells, CD45RA(low/-) CD4 T cells and monocytes. In multivariate analyses, the counts of the following subsets remained significantly inversely correlated with the infection rates: total B cells (P =.0004) and monocytes (P =.009). CD28(-) CD8 T-cell counts showed no correlation with infection rates. In conclusion, the susceptibility of patients to infections late posttransplant may be due in part to the slow reconstitution of B cells and monocytes.